This research will provide the scientific and engineering information upon which can be based the confident engineering design of automated laboratory analyses. Particular attention will be directed to the mucopolysaccharidoses-related connective tissue mucopolysaccharides (AMPS, acidic glycosoaminoglycans) and Cystic Fibrosis. The methodologies developed and the results obtained will be directly applicable to the automation of analyses for related clinical entities. Recent additions to the microscope, coupled with the use of molecular probes enable biophysical cytochemical investigations on biopolymers in their native state in living cells. These physical optical methods (microspectrofluorophotometry and microspectropolarimetry) can produce physical chemical data from as 10-17 moles. The data are such as to lead directly to an engineering design for automation of cytopathology, urine, and body fluids analyses, and analyses of micro samples (extracts). AMPS complex with fluorescent dyes which can serve as molecular probes. The physicochemical and optical properties of the dye-AMPS complex are characteristic of the particular complex and differ in general, from those of the free dye and other dye-substrate complexes. The characteristic alterations in the properties of the dye underlie the rationals for this research and are the common element uniting the participating disciplines. Specifically, physical chemical and biophysical cytochemical studies using identical molecular probes will be conducted in parallel to develop rapid, accurate, qualitative and quantitative analytical methodologies for connective tissue AMPS. Samples from normals and patients including amniocenteses will be examined. The experimental systems will be set-up with automation limited to essential features requiring validation. Recommendations for entering upon the engineering development and production for general use of particular automated analyses will be made as rapidly and as frequently as the research results warrant. The Science of Biophysical Cytochemistry and its methodologies are being applied to Human Uterine Cancer to provide a scientific basis for automating cytopathological analyses and to provide more basic scientific information on cancers associated with the Human female genital tract.